Oxidation, Disease and Aging

It turns out that oxidation, the same chemical reaction that causes iron to rust, plays a similarly corrosive role in our bodies. The process is called oxidative stress. The oxidation of oxidative stress gradually damages healthy cells and contributes to diseases ranging from Alzheimer's, heart disease and stroke to macular degeneration (the leading cause of adult blindness) and cancer. Oxidation has even been implicated in the aging process itself.

Oxidation can damage DNA, mitochondria, cell membranes and other mechanisms and structures essential to the cell. This kind of damage underlies many diseases, especially of the heart, lungs and brain, which are heavy users of oxygen.

Now, as reported in the journal Nature, University of Wisconsin-Madison scientists have discovered a gene expression pathway that exerts great influence over the process of oxidative stress in the human body.

This genetic mechanism seems to play a role in a host of medical conditions, raising the possibility that one day, scientists may be able to manipulate it to prevent many of the diseases that are accepted today as an inevitable part of growing old. "Most of the genes this pathway controls are important for human disease," says Richard A. Anderson of the UW School of Medicine and Public Health and senior author of the report. "This is a totally new and novel pathway that controls the synthesis of enzymes involved in many human diseases."

Oxidative stress occurs when the body's mechanism for neutralizing highly toxic chemicals known as free radicals is overtaxed. Free radicals perform some necessary functions within the body, but they can also participate in unwanted side reactions that cause cell damage. Many forms of cancer, for example, are thought to be the result of reactions between free radicals and DNA.

The Wisconsin researchers discovered that their newfound pathway contains a genetic "on-off" switch for a protein known as heme oxygenase-1; this protein protects cells from oxidative stress.

The discovery of a gene expression pathway that influences oxidative stress has tremendous clinical value, Anderson says, because it could potentially be manipulated to mitigate the damage oxygen does to cells.

"Oxidative stress control pathways for us humans are pretty important because we live in an environment where oxygen is required to keep us alive, but also stresses us because of oxidative damage to our cells," Anderson says.

Oxidation can damage DNA, mitochondria, cell membranes and other mechanisms and structures essential to the cell. This kind of damage underlies many diseases, especially of the heart, lungs and brain, which are heavy users of oxygen. Although the discovery of a new genetic pathway in cells is important, much work remains to identify how the pathway influences human disease, Anderson says.

"We've discovered a novel pathway that controls expression of genes important to oxidative stress," he says. "It has really key implications for heart disease, stroke, and possibly for aging, but it is still not clear precisely what functions this pathway is regulating in the context of those conditions."